The long-term goal of this project is to develop a novel SPECT system design that tackles one of the most limiting aspects of SPECT instrumentations by offering a greatly improved sensitivity without sacrificing imaging resolution. This proposed approach is based on the use of a novel detection system called dense- camera-array (DCA). As we have demonstrated with a Monte Carlo study described in Sec. C.2, a small animal SPECT system based on the DCA detectors could a photon detection efficiency of >1% (as compared to the typical levels of 0.1%-0.01% found in modern pre-clinical SPECT instrumentations), while maintaining an excellent spatial resolution. This dramatic increase in sensitivity could potentially provide a radical change in how we might employ SPECT imagining in both pre-clinical and (potentially) clinical practice, by offering a dramatically lowered detecton limit and allowing for new imaging procedures that would be difficult to implement with the current generation of SPECT instrumentations. The design of dense camera array (DCA) is inspired by the compound eyes often found on small invertebrates, such as flies and moths. A DCA camera consists of a large number of independent micro-pinhole-gamma- camera-elements closely packed in a dense array (e.g. 10-20 independent camera-elements per cm2). Each of the micro-camera-elements covers a narrow view angular through the object. When constructing a SPECT system with multiple DCAs, there will be a very large number (up to several thousand) of micro-camera- elements in the system pointing towards the object and collecting gamma rays simultaneously. This is the key for attaining a super-high detection efficiency, while maintaining an excellent imaging resolution. One of the key challenges for constructing the DCA camera is the need for a state-of-art detector technology that offers an ultrahigh 3-D spatial resolution (e.g. 100mm), an excellent energy resolution, an adequate count-rate capability and a very high stopping power for energetic gamma rays. This would allow us to pack 10-20 independent micro-camera-elements into 1 cm2 area, and to ensure each micro-camera-element having a sufficient resolving power. For this project, we will utilize a recently developed small-pixel CdTe/CZT detector equipped with a hybrid pixel-waveform readout system to construct the prototype DCA cameras.